Computational approaches to investigate hydrogen bonding and base stacking for A-U, G-U, and I-U pairs

CHED 962

Praneetha Thulasi, thulasip@slu.edu, Michael Lewis, LewisM5@slu.edu, and Brent M. Znosko, znoskob@slu.edu. Department of Chemistry, Saint Louis University, 3501 Laclede Ave., Saint Louis, MO 63103
Inosine is found in the anticodon loop of several tRNAs, results from the deaminatino of adenosine, and can be utilized in oligonucleotide probes. Surprisingly, there is little published data available on the thermodynamics, energetics, and structures of RNA motifs containing inosine. In order to characterize RNA oligomers containing inosine, a previous study performed optical melting experiments with inosine-containing ribonucleotides [Wright et al. 2007]. Surprisingly, duplexes containing a single, internal I∙U pair were, on average, 2.4 kcal/mol less stable than similar duplexes containing A-U pairs. Even more surprising, duplexes containing a single, internal I∙U pair were, on average, 2.0 kcal/mol less stable than similar duplexes containing G-U pairs. Two possible explanations for this observed discrepancy in energetics are differences in hydrogen bonding and/or stacking. This work uses computational approaches to investigate hydrogen bonding and base stacking for A-U, G-U, and I∙U pairs.